1,25(OH)_2D_3抑制高糖致大鼠肾脏系膜细胞肥大的机制研究  

Mechanism of 1,25-Dihydroxyvitamin D_3 inhibiting hypertrophy of glomerular mesangial cells induced by high dose glucose

作　　者：郑璞[1] 卓莉[1] 李隽[1] 李文歌[1] 

机构地区：[1]中日友好医院肾内科,北京100029

出　　处：《北京医学》2014年第2期92-95,共4页Beijing Medical Journal

基　　金：国家自然科学基金(81170675;81200537);国家科技支撑计划资助课题(2011BAI10B02)

摘　　要：目的观察1,25(OH)2D3能否抑制高糖导致的大鼠肾小球系膜细胞(RMC)肥大,并探讨其可能的作用机制。方法将体外培养的RMC分为正常对照组、等渗对照组、高糖组、单纯1,25(OH)2D3组、等渗+1,25(OH)2D3组及高糖+1,25(OH)2D3组。1,25(OH)2D3浓度为10-7mol/L,培养48 h,检测各组细胞总蛋白/细胞数比值,流式细胞仪检测各组前向角光强度(FSC),并采用Western blot检测各组维生素D受体(VDR)、哺乳动物雷帕霉素靶蛋白(mTOR)、核蛋白S6激酶(p70S6K)、延长因子4E结合蛋白(4EBP1)的表达情况。结果高糖+1,25(OH)2D3组与高糖组比较,FSC降低(530.7±15.6 vs.509.0±35.0,P<0.05)、总蛋白/细胞数比值降低(41.5±1.7 vs.49.9±1.1,P<0.05);Western blot半定量灰度分析显示,高糖组较正常对照组VDR下调,mTOR及p70S6K的蛋白水平上调(P<0.05);高糖+1,25(OH)2D3组较高糖组mTOR及p70S6K的蛋白水平均下调(P<0.05)。结论 1,25(OH)2D3可逆转高糖导致的RMC肥大,其机制可能是通过抑制mTOR及其下游信号通路,减少了蛋白质的合成。Objective To observe whether 1,25-Dihydroxyvitamin D3 [（1,25 （OH）2D3]ean inhibit high-glucose induced rat mesangial cells （RMC） hypertrophy, and investigate the possible mechanisms. Methods Mice were divided into six groups： the control group, the isotonic control group, the high glucose group, the simple 1,25 （OH）2D3 group, the isoton- ic±1,25（OH）2D3 group, the high glucose±1,25（OH）2D3 group, the concentration of 1,25（OH）2D3 was l0s mol/L. Forty-eight hours after incubation, the total protein/cell number ratio were examined, the forward scattering （FSC） intensity was measured by flow cytomytry and the protein expression of vitamin D receptor （VDR）, nlammalian target of rapamycin （roTOR）, 70 kDa ribosomal protein S6 kinase （p70S6K）, elongation factor 4E-binding proteinl（4EBP1） were tested by western blot. Results Compared with the high glucose group, the high glucose±l,25 （OH）2D3 group, FSC intensity declined （530.7±15.6 vs. 509±35.0, P 〈 0.05） significantly, the total protein/cell number ratio and the western blot band intensity were also declined （41.5_±1.7 vs. 49.9±1.1, P 〈 0.05） significantly. Compared to the control group, the VDR in the high glucose group, was down-regulated as well as mTOR and p70S6K was up-regulated （P 〈 0.05）. On the other hand, the high glucose±l,25 （OH）2D3 group had lower level of roTOR and p70S6K （P 〈 0.05） compared to the high glucose group. Conclusion 1,25 （OH）2D3 can reverse hypertrophy of RMC induced by high-glucose, and the possible mechanism is inhibiting roTOR signaling pathways.

关 键 词：1 25(OH)2D3 系膜细胞 高糖 肥大 

分 类 号：R587.2[医药卫生—内分泌]